Urinary tract infections (UTI) are among the most common bacterial infections, resulting in millions of medical visits and costing billions of dollars annually, with uropathogenic strains of Escherichia coli (UPEC) being a predominant pathogen that also leads often to recurrent UTIs.  In recurrent UTIs, UPECs operate by entering, replicating within and re-emerging from bladder epithelial cells.  The epithelial cell entry is facilitated by binding of UPEC adhesin proteins (FimHA), located at the tips of protein pili, to mannose moieties that are presented from the centers of 16-nm uroplakin complexes on the luminal surface of bladder epithelial cells.  Given this mechanism of action and the dimensions between the mannose binding sites, we have designed hybrid biologic-synthetic polymer nanoparticles of controlled sizes, shapes and internal morphologies that are capable of being conjugated with FimHA and carrying antimicrobial agents, as a unique strategy to treat UTIs.  Our primary interest is to develop nanoparticle carriers that bind and enter bladder epithelial cells to deliver antimicrobial agents directly to the niche occupied by these harbored bacteria.  This presentation will provide a progress report on our optimization of the synthetic nanoparticle structural and compositional parameters together with genetic engineering of the FimHA protein, to achieve enhancement of the FimHA conjugation to the nanoparticles, antimicrobial packaging, cell entry, and antimicrobial efficacy.

Bacterial adhesin protein-conjugated polymer nanoparticles as antimicrobial nanodevices that utilize bacterial modes of epithelial cell entry for effective treatment strategies

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.